Array-based outcome prediction in head and neck cancer

DESCRIPTION (provided by applicant): Head and neck squamous cell carcinoma (HNSCC) is the fifth most common malignancy worldwide, representing a major international health problem. These tumors constitute an anatomically heterogenous group of neoplasms, arising from diverse anatomic locations including the oral cavity, oropharynx, hypopharynx, larynx and nasopharynx. Treatment planning for HNSCC depends largely on anatomical staging of the disease at presentation. Conventional treatment with surgery and/or radiation therapy, and/or chemotherapy is associated with significant morbidity affecting speech, swallowing and overall quality of life. Despite these interventions, recurrence of the disease is observed in about 50% of patients, locally, regionally or at a distant site with high rates of associated mortality. There have been few identified molecular markers that can be reliably used in early detection of HNSCC or as indicators of prognosis. There is therefore an urgent need to identify prognostic molecular markers that can be used at the time of initial diagnosis to predict patient prognosis so that more appropriate treatments can be used at the outset to improve outcome. The goal of this highly collaborative research project is to identify the specific molecular events that predict tumor behavior and patient outcome in this disease by measuring variation in transcript abundance for at least 20,000 different genes in one hundred independent tumor samples. The specific aims of the project are: 1) To test the hypothesis that the pattern of global gene expression in a HNSCC clinical specimen contains information that can be used as a predictor of prognosis. We will apply cDNA expression array analysis and comparative genome hybridization (CGH) array analysis to a set of 100 HNSCC patient tumor samples using a human cDNA microarray containing 28,000 cDNA clones, 2) Combined data from these experiments will be used as a "learning set" to identify gene expression changes and genome copy number aberrations that correlate with histopathology, metastasis, clinical outcome and survival in these patients 3) We will assess the quantity and cellular distribution of the products of identified prognostic genes using immunohistochemical techniques with commercially available antibodies using a HNSCC tissue array constructed in the Department of Pathology and Montefiore Medical Center